Occlusive vascular disease culminating in coronary thrombosis and myocardial infarction is epidemic in our modern industrialized society. Among striving, stressed, middle age executives in the United States, for example, the disease accounts for more than fifty percent of all hospitalizations and more than thirty percent of all deaths.
Since the classical features of coronary heart attack have been so widely publicized, it is seldom realized that early and accurate diagnosis is frequently quite difficult. Only a minority of patients have electrocardiographic findings which are dramatically clear cut. All too often, when a coronary patient is first seen by a physician, the patient's history is garbled, the symptoms are distorted, the physical findings are inconclusive and the electrocardiogram is unhelpful. When retrospective analyses of serial electrocardiograms on patients with myocardial infarction are undertaken, it is almost invariably possible to discern changes from the initial (or presenting) EKG which may be interpreted as early indications of cardiac damage. This type of analysis permits a whole pattern of progressive and retrogressive EKG changes to be examined at once. But in actual practice, when the presenting EKG is taken within twelve hours of an acute attack, it is possible to recognize changes pathognomonic of an infarct in only about one-third of the cases in which the condition actually occurs. In addition, it should be noted that EKG abnormalities may occur in the absence of disease of any kind and that changes not significantly different from those of infarction may accompany anginal attacks, pericarditis, pulmonary embolus and several other conditions that may give rise to clinical uncertainty.
Physical and laboratory findings consistent with tissue necrosis are the rule rather than the exception in myocardial infarction. Fever, leucocytosis and elevation of the erythrocyte sedimentation rate (ESR) generally become apparent within 24 to 48 hours. Serum glutamic oxalacetic transaminase (SGOT) rises to a peak on the second or third day and, in the absence of an additional insult, falls fairly rapidly thereafter. Absolute values are not nearly as meaningful as sequential variations, however, and it must always be borne in mind that pulmonary embolus, liver disease, and a considerable number of other conditions may give rise to elevated SGOT values. Similarly, serum creatinine phosphokinase (CPK), lactic dehydrogenase (LDH), gamma glutamyl transpeptidase (.gamma. -GTP), serum pyruvate kinase (SPK) and their several isoenzymes may show a variety of elevations and changes throughout the course of a nonfatal myocardial infarction. The strength of the enzymatic tests lies primarily in their usefulness for monitoring the severity of the disease and the patient's progress toward recovery. But, interesting as these substances are to the laboratory scientists, medical practitioners have found them wanting and the search continues for a diagnostically meaningful biochemical signature of cardiac muscle injury. The fact is that, when help is most needed clinically--at the time of differential diagnosis, hospital admission and primary care--the laboratory findings are frequently no less equivocal than the signs and symptoms of coronary thrombosis.
When the heart muscle is damaged, particularly when necrosis occurs, a substance called myoglobin is very rapidly released. Because of its molecular structure, myoglobin soon finds its way via the kidneys from the blood stream to the urine. In patients with myocardial infarction, urinary myoglobin excretion generally rises to a maximum in the first twelve hours, diminishes rapidly in 24 hours and ordinarily reverts to undetectable levels in less than five days. On account of the very transitory nature of measurable levels of myoglobin excretion, it might appear at first glance improbable that a quantitative test for the substance could compete with the conventional enzyme tests and EKGs as a guide to the extent of myocardial damage. But, on account of the unusual speed with which urinary myoglobin excretion follows cardiac muscle injury, it does provide a reliable "yes-no" test and, when set at an appropriate level of sensitivity, it can serve as an extremely useful aid to the diagnosis of myocardial infarction. This is true even though urinary myoglobin excretion is not exclusive to myocardial infarction and may be associated with muscular dystrophy, crush (wringer) type injuries, alcoholism, epileptic seizures and a number of other conditions (most of which are quite readily distinguishable clinically from cardiac muscle damage).
A sensitive urinary myoglobin test can also bring to light subclinical infarcts that might otherwise be passed off as severe anginal attacks. Since these "occult" or mini-infarcts are believed to be often the progenitors of a more extensive and possibly fatal infarct-to-come, their detection could serve as a signal for the prompt institution of strict bed-rest and other therapy calculated to avert an impending disaster. Another possible use of a urinary myoglobin test is based on the theoretical likelihood that the substance may be released from skeletal muscle in cases of deep vein thrombosis. Thus, in nonsurgery associated cases the test could very well facilitate differentiation of this difficult-to-diagnosis infliction from other conditions. Accordingly, a need has existed for the development of a urinary myoglobin test to serve as a meaningful diagnostic tool which would help to confirm the presence of cardiac muscle damage in suspect or equivocal cases of myocardial infarction. In particular, a quick, convenient "yes-no" test has been needed in place of the more cumbersome and sophisticated quantitative systems which have been used to date.
Both chemically and physically, myoglobin closely resembles the oxygen carrying blood pigment hemoglobin. The most significant difficulty with the detection of myoglobin in the presence of hemoglobin is that both myoglobin and hemoglobin will react with the usual reagents for detection of peroxidase-like substances which could otherwise be utilized for the detection of myoglobin.